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September 2012

OSA Increases Cardiovascular Mortality in the Elderly

Untreated severe obstructive sleep apnea (OSA) is associated with an increased risk of cardiovascular mortality in the elderly, and adequate treatment with continuous positive airway pressure (CPAP) may significantly reduce this risk, according to a new study from researchers in Spain.

“Although the link between OSA and cardiovascular mortality is well established in younger patients, evidence on this relationship in the elderly has been conflicting,” said lead author Miguel Ángel Martínez-García, MD, of La Fe University and Polytechnic Hospital in Valencia, Spain. “In our study of 939 elderly patients, severe OSA not treated with CPAP was associated with an increased risk of cardiovascular mortality especially from stroke and heart failure, and CPAP treatment reduced this excess of cardiovascular mortality to levels similar to those seen in patients without OSA.”

The findings were published online ahead of print publication in the American Thoracic Society’s American Journal of Respiratory and Critical Care Medicine.

All subjects in this prospective, observational study were 65 years of age or older. Median follow-up was 69 months. Sleep studies were conducted with either full standard polysomnography or respiratory polygraphy following Spanish guidelines. OSA was defined as mild-to-moderate (apnea-hypopnea index [AHI] 15-29) or severe (AHI ≥30). Patients with AHI <15 acted as controls. CPAP use ≥4 hours daily was considered as good adherence to treatment.

Compared with the control group, the adjusted hazard ratios for cardiovascular mortality were 2.25 (CI, 1.41 to 3.61) for patients with untreated severe OSA, 0.93 (CI, 0.46 to 1.89) for patients treated with CPAP and 1.38 (CI, 0.73 to 2.64) for patients with untreated mild-to-moderate OSA. Similar results were observed among the subgroup of patients ≥75 years of age. Among patients who initiated CPAP treatment, compliance was independently associated with a reduced risk of cardiovascular mortality.

The study had a few limitations, including that the study was not randomized, the reduced statistical power in the subgroup analyses, and the use of respiratory polygraphy to diagnose OSA in a number of patients. Strengths included being the large study size including exclusively elderly patients and the long follow-up.

“This is the first large-scale study to examine the impact of OSA on cardiovascular mortality in a series including exclusively elderly patients and assess the effectiveness of CPAP treatment in reducing this risk,” said Dr. Martínez-García. “Our finding that adequate CPAP treatment is associated with significant reductions in cardiovascular mortality in patients with OSA has important implications, especially given the increasing elderly population.”

To read the article in full, please visit: http://www.thoracic.org/about/newsroom/press-releases/resources/Martinez-Garcia.pdf.

About the American Journal of Respiratory and Critical Care Medicine: With an impact factor of 11.080, the AJRRCM is a peer-reviewed journal published by the American Thoracic Society. It aims to publish the most innovative science and the highest quality reviews, practice guidelines and statements in the pulmonary, critical care and sleep-related fields. Founded in 1905, the American Thoracic Society is the world's leading medical association dedicated to advancing pulmonary, critical care and sleep medicine. The Society’s 15,000 members prevent and fight respiratory disease around the globe through research, education, patient care and advocacy.

Contact for article: Miguel Ángel Martínez-García, Pneumology Service, La Fe University and Polytechnic Hospital. Valencia, Spain, Bulevar Sur s/n 46006-Valencia Phone: +34-609865934 Email: m.a.martinez@saludalia.com or miangel@comv.es

Antibiotics Improve Exacerbations of Mild-to-Moderate COP

Antibiotic treatment with amoxicillin/clavulanate improves moderate exacerbations in patients with mild-to-moderate chronic obstructive pulmonary disease (COPD) and significantly prolongs the time between exacerbations, according to a new study from researchers in Spain.

“The existing evidence for antibiotic therapy in non-severe exacerbations of COPD is weak,” said lead author Carl Llor, MD, PhD of the University Rovira i Virgili in Tarragona, Spain. “The results of our multicenter, randomized, double-blind, placebo-controlled trial show that antibiotic treatment is more effective than placebo in these patients, with an absolute difference in cure rates of 14.2%, and that the median time to next exacerbation is prolonged with antibiotic treatment, compared with placebo, from 160 to 233 days.”

The findings were published online ahead of print publication in the American Thoracic Society’s American Journal of Respiratory and Critical Care Medicine.

A total of 310 patients were enrolled in the study and randomized to receive either amoxicillin/clavulanate (500/125 mg) or placebo three times daily for eight days. All participants were at least 40 years old and had a spirometrically-confirmed diagnosis of mild-to-moderate COPD. The primary endpoint was clinical cure at the end of therapy visit.

A total of 117 patients in the amoxicillin/clavulanate group (74.1%) and 91 in the placebo group (59.9%) were considered cured at follow-up. Median time to next exacerbation was significantly longer in the amoxicillin/clavulanate group. Clinical success, defined as either cure or improvement, was achieved in 90.5% of the antibiotic-treated group, compare with 80.9% of the placebo group. Capillary C-reactive protein (CRP) at a cutoff of 40 mg/l was found to be an excellent predictor of clinical outcome; patients with CRP levels below 40 mg/l were significantly more likely to be cured without the use of antibiotics.

The study had a few limitations, including a limited sample size and the lack of objective assessment of symptom resolution at follow-up, other than peak flow measurements.

“The clinical success rate we saw with amoxicillin/clavulanate treatment in our patients with mild-to-moderate COPD is higher than what has been seen in previous placebo-controlled trials which included patients with severe COPD,” Dr. Llor said. “This suggests an effect of the severity of airflow obstruction on the rate of treatment success.”

“We have shown that antibiotic treatment is superior to placebo in improving exacerbations in mild-to-moderate COPD,” Dr. Llor concluded. “Many of these patients are treated in primary care settings, and our study supports the use of antibiotics to treat mild to moderate airway obstruction, mainly in patients with elevated CRP levels.”

To read the article in full, please visit: http://ajrccm.atsjournals.org/content/early/2012/08/22/rccm.201206-0996OC.abstract.

Contact for article: Carl Llor, c. FelipPedrell, 45-47. 43005 Tarragona, Spain, Phone: +34 671085857, Email: carles.llor@urv.cat

Cystic Fibrosis Patients of Low Socioeconomic Status Are Less Likely to be Accepted for Lung Transplant

Adult cystic fibrosis (CF) patients of low socioeconomic status (SES) have a greater chance of not being accepted for lung transplant after undergoing initial evaluation, according to a new study.

“While earlier studies have indicated that SES does not affect access to care for cystic fibrosis, ours is the first study to examine the relationship between SES and access to lung transplantation in these patients,” said lead author Bradley S. Quon, MD, MSc, MBA, of the University of Washington Medical Center in Seattle. “In our nationally representative sample of adult patients with CF, we found that multiple indicators of SES were associated with greater odds of not being accepted for transplant.”

The findings were published online ahead of print publication in the American Thoracic Society’s American Journal of Respiratory and Critical Care Medicine.

The study included 2,167 adult CF patients from the CF Foundation Patient registry, all of whom underwent their first lung transplant evaluation as an adult between January 1, 2001, and December 31, 2009. Receipt of Medicaid insurance was used as the primary indicator of SES status. The outcome of interest was acceptance onto the waiting list for lung transplant after initial evaluation. Patients who were either declined or deferred were classified as not accepted, and an additional sensitivity analysis was performed based on the final decision of whether a patient was accepted or declined at the end of the study period.

Of the 2,167 patients included in the study, 1009 (47%) received Medicaid. Compared to non-Medicaid patients, the odds of not being accepted for lung transplant was 1.56 fold higher among Medicaid recipients. This relationship was independent of differences in disease severity, demographic factors, contraindications to lung transplant, and use of the lung allocation score.

Other indicators of low SES, including residing in lower income zip codes and not graduating from high school, were also independently associated with not being accepted for lung transplant after undergoing initial evaluation.

The study had a few limitations, including the use of Medicaid and other indicators as proxies for SES status. Furthermore, inadequate social support and poor adherence are key determinants of transplant eligibility. Although the authors attempted to account for these factors in their analysis, incomplete adjustment for these variables may at least partially explain why low SES was associated with not being accepted for lung transplant.

“The results of our study are concerning, as the effects of SES status on access to lung transplant appear to be unrelated to differences in disease severity or potential contraindications,” said Dr. Quon. “More research is needed to explore the factors associated with Medicaid status that negatively impact lung transplant access and to assess whether these disparities are seen in other pre-lung transplant patient populations.”

To read the article in full, please visit: http://www.thoracic.org/about/newsroom/press-releases/resources/Quon.pdf.

Contact for article: Bradley S. Quon, MD, MSc, MBA; University of Washington Medical Center, BB-1327, 1959 NE Pacific St., Seattle, Washington, 98195, United States

Email:  bquon@uw.edu